Hanna Sanoff, MD, MPH is a medical oncologist at the University of Virginia specializing in the care of patients with gastrointestinal malignancy. Dr. Sanoff's long-term goal is to lead a health services research program dedicated to investigating the use and comparative effectiveness (CE) of emerging therapies for GI cancer. Dr. Sanoff has a solid foundation in clinical trials research obtained through mentored research and structured professional development supported by NIH programs for young investigators (K30, K12) at the University of North Carolina. The research proposed for this award forms the core of a five year career development program that will be integrated with didactic training in epidemiology, biostatistics, and health services research content, all with the goal of honing the skills Dr. Sanoff will need to be an independent CE researcher. The mentorship team is a complementary pair of national leaders in liver transplantation and health services research, each of whom has had success as an NIH-funded investigator and mentor. An advisory team of senior leaders will help oversee Dr. Sanoff's professional academic development. UVA's academic excellence in liver transplantation and hepatocellular carcinoma (HCC) are ideally suited to support the proposed research project. HCC is a deadly disease with a rising incidence and mortality in the US. HCC is a largely understudied disease that disproportionately affects the poor and patients of racial and ethnic minorities. Although multiple treatments are routinely used for HCC, few prospective trials have tested their efficacy and even less in known of their real world effectiveness outside a small handful of specialized centers. The focus of the scientific proposal is to evaluate the use and CE of nonsurgical therapies for HCC. Aim 1 will evaluate the CE of HCC treatment given to patients awaiting liver transplantation through a multicenter retrospective series. This primary data collection will allow us to evaluate the effect of specific treatment practices and response to therapy that are not available in observational datasets. Aim 2 will evaluate the safety of on-waitlist therapies for HCC by comparing rates of adverse outcomes by treatment through a linkage of Medicare claims to patient records in the Scientific Registry of Transplant Recipients. Together Aims 1 and 2 will form the basis for subsequent prospective and decision model work in on-waitlist therapy in HCC patients. In Aim 3, SEER- Medicare and a novel linkage between North Carolina Central Cancer Registry and Blue Cross and Blue Shield claims will be used to describe use and outcomes of the newest HCC treatment, sorafenib, in clinically relevant subgroups of HCC patients. Relevance: Results of these aims will serve to directly inform the care of the steadily increasing population of patients with HCC. Successful completion of the proposed career development plan will provide Dr. Sanoff with an uncommon combination of skills in CE research and clinical trials. With her clinical expertise in hepatocellular carcinoma, she would be a unique position to further the research agenda of this deadly disease.